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Alkaloids

9. NAMING OF ALKALOIDS Numerous

methods can be used to name alkaloids 1-

Generic plant name –atropine from Atropa

belladonna 2-Specific name of the plant –

cocaine from Erythroxylum coca. 3-

Common name of the herb –ergotamine

from ergot (rye) 4-Physiological action of

the plant –emetine producing emesis 5-

Other –e.g. morphine derived from ancient

Greek mythology –Morpheus –god of

dreams

10. EXTRACTION OF ALKALOIDS

Extraction is based on the basicity of

alkaloids and on the fact that they normally

occur in plants as salts (i.e.: on the

solubility of bases and salts in water and

organic solvents). Herbs often contain

other materials which can interfere with

extraction such as large amounts of fat,

waxes, terpenes, pigments and other

lipophilic substances (e.g by forming

emulsions) –avoided by defatting the

crushed herb (using petroleum ether and

hexane. Extraction method normally

depends on the raw material, the purpose

of extraction & the scale on which is to be

performed. For research purposes:

Definition

Alkaloids are basic nitrogen containing

compounds. They are generally obtained from

plants, animals and microorganisms and

often demonstrate a marked physiological action

ALKALOID DESCRIPTION

Contains nitrogen -usually derived from an amino acid.

Bitter tasting, generally white solids (exception -nicotine is a brown

liquid).

They give a precipitate with heavy metal iodides.

Caffeine, a purine derivative, does not precipitate like most alkaloids.

Alkaloids are basic -they form water soluble salts. Most alkaloids are

well-defined crystalline substances which unite with acids to form

salts. In plants, they may exist

in the free state,

as salts or

as N-oxides.

Occur in a limited number of plants. Nucleic acid exists in all plants,

whereas, morphine exists in only one plant species .

TESTS FOR ALKALOIDS

Most alkaloids are precipitated from neutral or

slightly acidic solution by

Dragendorff's reagent (solution of potassium

bismuth iodide)orange coloured precipitate.

Mayer's reagent (potassio mercuric iodide

solution) Cream coloured precipitate.

Wagner’s reagent (iodine in potassium iodide)

red-brown precipitate

Hagers reagent (picric acid) yellow precipitate

Caffeine does precipitate

OCCURRENCE, DISTRIBUTION& LOCATION OF

ALKALOIDS

Occur in bacteria(Pseudomonas aeruginosa) and

rarely in fungi (pscilocin from hallucinogenic

mushrooms).

Some alkaloids occur in several genera from

different species (caffeine), but most occur in closely

related species.

Some occur in certain families (hyoscyamine), while

others occur only in a specific species (morphine).

Rarely do plants contain more than 1 type of

alkaloid.

All alkaloids of one plant will have a common

biogenenetic origin

• Alkaloids occur in all plant

parts, but are usually

localized in one organ (e.g.

the bark or seeds).

• Within the plant, [alkaloid]

can vary widely from part to

part –some parts may contain

no alkaloids.

• Occasionally, different

alkaloids also form in different

parts of the plant.

• Alkaloid concentrations occur

in wide ranges –e.g.

Madagascar periwinkle

contains 3g per (anti-cancer)

alkaloids per tonne of leaves

PHYSICAL-CHEMICAL PROPERTIES OF ALKALOIDS

MW: 100 –900

Most bases which do not contain O2 are liquid at

room temperature (nicotine), while those that do are

solids. In rare cases they are coloured.

Most solid bases rotate the plane of polarized light,

have high melting points.

Normally are not soluble in water (occasionally

slightly soluble).

Soluble in a polar or slightly polar organic solvents.

Soluble in concentrated hydroalcoholic solutions

The basicity of alkaloids depends on the availability

of the lone pair of e-on the N2 atoms: e-donating

groups enhance basicity, while e-withdrawing groups

decrease it.

Because some alkaloids have a carbonyl group on

the amide, they can also be neutral (colchicine &

piperine).

Basic characteristic renders complex alkaloids

unstable, so that in solution they are sensitive to

heat, light & oxygen.

Basic character of alkaloids also allows them to form

salts with mineral acids (such as hydrochlorides,

nitrates and sulphates) or inorganic acids (tartrates,

sulfamates).

Alkaloid salts are soluble in water and dilute alcohols.

Solid salts can be conserved well and are a common

NAMING OF ALKALOIDS

Numerous methods can be used to name alkaloids

1-Generic plant name –atropine from Atropa belladonna

2-Specific name of the plant –cocaine from

Erythroxylum coca.

3-Common name of the herb –ergotamine from ergot

(rye)

4-Physiological action of the plant –emetine producing

emesis

5-Other –e.g. morphine derived from ancient Greek

mythology –Morpheus –god of dreams

EXTRACTION OF ALKALOIDS

Extraction is based on the basicity of alkaloids and on the fact that

they normally occur in plants as salts (i.e.: on the solubility of bases

and salts in water and organic solvents).

Herbs often contain other materials which can interfere with extraction

such as large amounts of fat, waxes, terpenes, pigments and other

lipophilic substances (e.g by forming emulsions) –avoided by

defatting the crushed herb (using petroleum ether and hexane.

Extraction method normally depends on the raw material, the purpose

of extraction & the scale on which is to be performed.

For research purposes: chromatography allows for quick and reliable

results.

If larger amounts of alkaloids need to be extracted, one of the

following methods can be used.

GENERAL METHOD

• Powdered, defatted herb is mixed

with an alkaline aqueous solution.

• Free bases are then extracted

with organic solvents.

• Normally aqueous ammonia is

used, but a carbonate solution is

used when alkaloids contain

fragile elements such as a ester

or lactone.

• In some cases, e.g. Cinchona

bark, a mixture of calcium

hydroxide & sodium hydroxide

should be used as the alkaloids

are bound to tannins.

• Organic solvent: chloroform,

dichloromethane or ethyl acetate

–depends on the toxicity, safety,

cost & ease of recovery and

Step II

Organic solvent containing alkaloids

(bases) is separated from residue &

concentrated by distillation under

pressure if needed.

Solvent is stirred with an acidic

aqueous solution: alkaloids go into the

solution as salts. Impurities remain in

the organic phase.

• Aqueous solution of alkaloid

salts is washed with an apolar

solvent (hexane)

• Alkalinized with a base using

an organic solvent not

miscible with water.

• Alkaloids precipitate and

dissolve in the organic phase.

• Extraction of aqueous phase

continues till all alkaloids have

moved into the organic phase

(tested when Mayer’s reaction

on the aqueous phase

becomes negative).

• This purification step may be

carried out in a separation

funnel or in centrifugal

extractors

Step III

Organic solvent containing alkaloid bases is

decanted, freed from water traces (drying over

anhydrous salt e.g. sodium sulphate) and evaporated

under reduced pressure.

A dry residue remains: total basic alkaloids.

Extraction of liquid alkaloids

2 Methods possible

1-Plant powder is extracted directly

with acidified water

2-Plant powder is extracted with

acidified alcoholic or a hydroalcoholic

solution. This is then followed by

distillation under vacuum (eliminates

that alcohol, leaving behind and acidic

aqueous solution of alkaloid salts)

Classification of

Alkaloids1. Biological origin

Sedatives : Morphine

Vasodilatation : Ephedrine, Ergonovine

.

Local anesthetic : Cocaine

Hallucinating : Mescaline, Psilocybin.

2-Biosynthetic pathway

Ornithine- Tropane, Pyrrolidine, Pyrrolizidine

Tyrosine-Benzyl isoquinoline

Tryptophane- Indole alkaloids, Quinoline

Pyridine- Pyridine

Lysine- Quinolizidine, Piperidine

3- Chemical classification

True (Typical) alkaloids that are derived from amino acids and have nitrogen in a heterocyclic ring. e.g Atropine

Proto alkaloids that are derived from amino acids and do not have nitrogen in a heterocyclic ring. e.g Ephedrine

Pseudo alkaloids that are not derived from amino acids but have nitrogen in a heterocyclic ring. e.g Caffeine

False alkaloids are non alkaloids give false positive reaction with alkaloidal reagents.

A. Proto alkaloids

These are also called Non heterocyclic or Atypical

alkaloids or Biological amines.

These are less commonly found in nature.

These molecules have a nitrogen atom which is

not a part of any ring system.

Examples of these include ephedrine, colchicine,

erythromycin and taxol etc.

Table below shows the chemical structure and

biological significance of these compounds:

Name Structure Biological

Significance

Ephedrine

Adrenergic agent-

used for asthma and

hay fever

Colchicine

Relieves gout

Erythromycin

Antibiotic

Taxol

(Paclitaxel)

Used in the treatment

of ovarian cancer,

breast cancer and

non-small cell lung

cancer

B. Heterocyclic Alkaloids or Typical Alkaloids:

Structurally these have the nitrogen as a part of a

cyclic ring system.

These are more commonly found in nature.

Heterocyclic alkaloids are further subdivided into

14 groups based on the ring structure containing

the nitrogen

No. Heterocycle Example

1.

Pyrrole and

Pyrrolidine

Hygrine, Stachydrine

2.

Pyrrolizidine

Senecionine, Symphitine, Echimidine,

Seneciphylline

3.

Pyridine and Piperidine

Lobeline, Nicotine, Piperine, Conine,

Trigonelline

4.

Tropane (piperidine/N-methyl-

pyrrolidine)

Cocaine, Atropine, Hyoscyamine, Hyoscine

5.

Quinoline

Quinine, Quinidine, Cinchonine,

Cinchonidine

6.

Isoquinoline

Morphine, Emetine, Papaverine, Narcotine,

Tubocurarine, Codeine

7.

Aporphine (reduced

isoquinoline/naphthalene)

Boldine

8.

Quinolizidine

Lupanine, Cytisine, Laburnine, Sparteine

9.

Indole or

Benzopyrole

Ergometrine, Vinblastine, Vincristine, Strychnine, Brucine,

Ergotamine, Yohimbine, Reserpine, Serpentine,

Physostigmine

10.

Indolizidine

Castanospermine, Swainsonine

11.

Imidazole or

glyoxaline

Pilocarpine, Pilosine

12.

Purine (pyrimidine/imidazole)

Caffeine, Theobromine

13. Steroidal (some combined as

glycosides)*

Conessine, Solanidine

14. Terpenoid*

Aconitine, lycaconitine, Aconine

*Note- Steroidal and terpenoid classes are also treated as separate classes or along with glycosides.